RELATIONSHIP BETWEEN EVOLUTIONARY RATE AND CELLULAR LOCATION AMONG THE INV SPA INVASION PROTEINS OF SALMONELLA-ENTERICA/

For 21 strains of Salmonella enterica, nucleotide sequences were obtai ned for three invasion genes, spaO, spaP, and spae, of the chromosomal inv/spa complex, the products of which form a protein export system r equired for entry of the bacteria into nonphagocytic host cells. These genes are present in all eight subspecies of the salmonellae, and hom ologues occur in a variety of other bacteria, including the enteric pa thogens Shigella and Yersinia, in which they are plasmid borne. Evolut ionary diversification of the invasion genes among the subspecies of S . enterica has been generally similar in pattern and average rate to t hat of housekeeping genes. However, the range of variation in evolutio nary rate among the invasion genes is unusually large, and there is a relationship between the evolutionary rate and cellular location of th e invasion proteins, possibly reflecting diversifying selection on exp orted proteins in adaptation to variable host factors in extracellular environments. The SpaO protein, which is hypervariable in S. enterica and exhibits only 24% sequence identity with its homologues in Shigel la and Yersinia, is secreted. In contrast, the membrane-associated pro teins SpaP, SpaQ, and InvA are weakly polymorphic and have >60% sequen ce identity with the corresponding proteins of other enteric bacteria. Acquisition of the inv/spa genes may have been a key event in the evo lution of the salmonellae as pathogens, following which the invention of flagellar phase shifting facilitated niche expansion to include war m-blooded vertebrates.